10-114212623-G-A

Position:

• chr10-114212623-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395205.1(TDRD1):​c.1831+587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,004 control chromosomes in the GnomAD database, including 5,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5118 hom., cov: 32)
• Consequence: TDRD1 NM_001395205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

Genes affected

TDRD1 (HGNC:11712): (tudor domain containing 1) This gene encodes a protein containing a tudor domain that is thought to function in the suppression of transposable elements during spermatogenesis. The related protein in mouse forms a complex with piRNAs and Piwi proteins to promote methylation and silencing of target sequences. This gene was observed to be upregulated by ETS transcription factor ERG in prostate tumors. [provided by RefSeq, Sep 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD1	NM_001395205.1	c.1831+587G>A		intron_variant		ENST00000695399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD1	ENST00000695399.1	c.1831+587G>A		intron_variant			NM_001395205.1	P4
TDRD1	ENST00000251864.7	c.1831+587G>A		intron_variant		1		A2
TDRD1	ENST00000369280.1	c.1831+587G>A		intron_variant		5		A2
TDRD1	ENST00000369282.5	c.1831+587G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38239 AN: 151886 Hom.: 5097 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38314 AN: 152004 Hom.: 5118 Cov.: 32 AF XY: 0.249 AC XY: 18527 AN XY: 74302

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.0728

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.246

Alfa AF: 0.246 Hom.: 603

Bravo AF: 0.257

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10510001; hg19: chr10-115972382;